Chiral enatiomerically pure 1,4-diols of type A (see Scheme I below; R=organic moieties) have been utilized in the synthesis of ligands, with the DuPHOS- and BPE-ligands constituting a particular well known example (Burk, M. J. J. Amer. Chem. Soc. 1991, 113, 8518). Despite of their relatively simple structure, there are only few methods known for their synthesis. One approach utilises the Kolbe-coupling of enantiomerically pure 3-hydroxy alkanoates (Burk, M. J., Feaster, J. E.; Harlow, R. L.; Tetrahedron: Asymmetry 1991, 2, 569). Another approach utilizes the enantioselective reduction of 1,4-diketones (Quallich, G. J., Keavey, K. N., Woodall, T. M. Tetrahedron Lett. 1995, 36, 4729), the douple alkylation of enantiopure 1,2-5,6-diepoxy hexane (Machinaga, N., Kibayashi, C. Tetrahedron Lett. 1990, 31, 3637), or the multistep functionalisation of carbohydrate derivatives (see for example: Stürmer R., Börner A., Holz J., Voss G. U.S. Pat. No. 6,043,396).

Diols of type B have so far not been used in the synthesis of ligands. An approach for obtaining these diols is provided by the reaction of phthaldialdehyde with an organo-zink reagent (see Scheme II below; Kleijn, H., Jastrzebski, T. B. H., Boersma, J., Koten, G. van Tetrahedron Lett 2001, 42, 3933). In the presence of a chiral ligand, the addition stops after the uptake of one equivalent of the organozink reagent to form the hemiacetal 2 with an enantiomeric excess (ee) of up to 80%. When a Grignard reagent is added into the mixture containing 2, a mixture of enantio-enriched chiral diol 3 and meso-diol 4 is formed. The process is attractive insofar that the desired chiral diol 3 can be obtained in a one-pot reaction. However, the starting material 1 is not readily available in large quantities, and the handling of organozink derivatives is difficult and there is only a limited range of these compounds available in commercial quantities. Moreover, diols of type 3 obtained according to this protocol have high ee's up to 85% but are not enantio-pure. Thus, apart from the need to separate 3 from 4, there is also the need to upgrade the ee of 3 to enantiopurity.

Thus there is a need for novel approaches for the synthesis of C2-symmetric 1,4-diols that allows for obtaining enantiomer pure compounds with a high ee and/or that allow to avoid the disadvantages mentioned above. It is the problem of the present invention to provide a solution manifesting such a novel approach.
Enantiopure 1,4-diols of type A (see for example U.S. Pat. No. 5,021,131) are essential intermediates in the manufacture of chiral ligands such as the BPE-ligands (U.S. Pat. No. 5,008,457) or the DuPHOS-ligands (U.S. Pat. No. 5,171,892). So far, these and related ligands (see EP1082328, U.S. Pat. No. 6,576,772 or WO 03/031456) have been prepared essentially as follows: In the first step the alcohols are activated by a leaving group such as a sulfonate or a cyclic sulfate. In the next step, the activated alcohols are reacted with a phosphine anion where in a nucleophilic SN2 displacement a phosphorus-carbon bond is formed with inversion at the carbon. In order to obtain the phospholane ligand with high optical purity, it is crucial that the optical yield for this displacement is very high.

There are numerous examples for clean SN2 displacements of the above type with aliphatic sulfonates or sulfates as leaving group. However, problems arise when the leaving group is in a benzylic position. Both sulfonates or sulfates derived from benzylic alcohols are labile, and the displacement is prone to follow a SN1 pathway with loss of chirality (see Org. Lett. 2003, 5, 1273 and references 8a and 8b therein). This is also true for halides as the leaving group, see EP 2 068 526. The present application also provides a solution to overcome these problems.